Manufacturing CD20/CD19-targeted iCasp9 regulatable CAR-TSCM cells using a Quantum pBac-based CAR-T engineering system.

Autor: Chang PS; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Chen YC; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Hua WK; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Hsu JC; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Tsai JC; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Huang YW; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Kao YH; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Wu PH; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Wang PN; Division of Hematology, Chang Gung Medical Foundation, Linkou Branch, Taipei City, Taiwan (R.O.C.)., Chang YF; Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (R.O.C.).; Department of Medical Research, Laboratory of Good Clinical Research Center, Mackay Memorial Hospital, Tamsui District, New Taipei City, Taiwan (R.O.C.).; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (R.O.C.)., Chang MC; Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (R.O.C.)., Chang YC; Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (R.O.C.).; Department of Medical Research, Laboratory of Good Clinical Research Center, Mackay Memorial Hospital, Tamsui District, New Taipei City, Taiwan (R.O.C.)., Jian SL; OBI Pharma, Inc., Taipei, Taiwan (R.O.C.)., Lai JS; OBI Pharma, Inc., Taipei, Taiwan (R.O.C.)., Lai MT; OBI Pharma, Inc., Taipei, Taiwan (R.O.C.)., Yang WC; OBI Pharma, Inc., Taipei, Taiwan (R.O.C.)., Shen CN; Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan (R.O.C.).; Genomics Research Center, Academia Sinica, Taipei, Taiwan (R.O.C.)., Wen KK; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.)., Wu SC; GenomeFrontier Therapeutics TW Co., Ltd., Taipei City, Taiwan (R.O.C.).
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 27; Vol. 19 (8), pp. e0309245. Date of Electronic Publication: 2024 Aug 27 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0309245
Abstrakt: CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.
Competing Interests: GenomeFrontier Therapeutics TW Co., Ltd. funded the study and played a crucial role in the study design, data collection and analysis, decision to publish, and preparation of the manuscripts. The coauthors – Peter S. Chang, Yi-Chun Chen, Wei-Kai Hua, Jeff C. Hsu, Jui-Cheng Tsai, Yi-Wun Huang, Yi-Hsin Kao, Pei-Hua Wu, Kuo-Lan Karen Wen, and Sareina Chiung-Yuan Wu – are affiliated with GenomeFrontier Therapeutics TW Co., Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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